Protection against Clostridioides difficile disease by a naturally avirulent C. difficile strain.

Autor:	Dong Q; Department of Medicine, University of Chicago, Chicago, Illinois, USA.; Duchossois Family Institute, University of Chicago, Chicago, Illinois, USA., Harper S; Duchossois Family Institute, University of Chicago, Chicago, Illinois, USA., McSpadden E; Duchossois Family Institute, University of Chicago, Chicago, Illinois, USA., Son SS; Department of Medicine, University of Chicago, Chicago, Illinois, USA.; Interdisciplinary Scientist Training Program, University of Chicago, Chicago, Illinois, USA., Allen MM; Department of Microbiology and Infectious Diseases, Université de Sherbrooke, Sherbrooke, Quebec, Canada., Lin H; Duchossois Family Institute, University of Chicago, Chicago, Illinois, USA., Smith RC; Duchossois Family Institute, University of Chicago, Chicago, Illinois, USA., Metcalfe C; Duchossois Family Institute, University of Chicago, Chicago, Illinois, USA., Burgo V; Duchossois Family Institute, University of Chicago, Chicago, Illinois, USA., Woodson C; Duchossois Family Institute, University of Chicago, Chicago, Illinois, USA., Sundararajan A; Duchossois Family Institute, University of Chicago, Chicago, Illinois, USA., Rose A; Duchossois Family Institute, University of Chicago, Chicago, Illinois, USA., McMillin M; Duchossois Family Institute, University of Chicago, Chicago, Illinois, USA., Moran D; Duchossois Family Institute, University of Chicago, Chicago, Illinois, USA., Little J; Duchossois Family Institute, University of Chicago, Chicago, Illinois, USA., Mullowney M; Duchossois Family Institute, University of Chicago, Chicago, Illinois, USA., Sidebottom AM; Duchossois Family Institute, University of Chicago, Chicago, Illinois, USA., Shen A; Department of Molecular Biology and Microbiology, Tufts University, Boston, Massachusetts, USA., Fortier LC; Department of Microbiology and Infectious Diseases, Université de Sherbrooke, Sherbrooke, Quebec, Canada., Pamer EG; Department of Medicine, University of Chicago, Chicago, Illinois, USA.; Duchossois Family Institute, University of Chicago, Chicago, Illinois, USA.; Interdisciplinary Scientist Training Program, University of Chicago, Chicago, Illinois, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 May 07. Date of Electronic Publication: 2024 May 07.
DOI:	10.1101/2024.05.06.592814
Abstrakt:	Clostridioides difficile (C. difficile) strains belonging to the epidemic BI/NAP1/027 (RT027) group have been associated with increased transmissibility and disease severity. In addition to the major toxin A and toxin B virulence factors, RT027 strains also encode the CDT binary toxin. Our lab previously identified a toxigenic RT027 isolate, ST1-75, that is avirulent in mice despite densely colonizing the colon. Here, we show that coinfecting mice with the avirulent ST1-75 and virulent R20291 strains protects mice from colitis due to rapid clearance of the virulent strain and persistence of the avirulent strain. Although avirulence of ST1-75 is due to a mutation in the cdtR gene, which encodes a response regulator that modulates the production of all three C. difficile toxins, the ability of ST1-75 to protect against acute colitis is not directly attributable to the cdtR mutation. Metabolomic analyses indicate that the ST1-75 strain depletes amino acids more rapidly than the R20291 strain and supplementation with amino acids ablates ST1-75's competitive advantage, suggesting that the ST1-75 strain limits the growth of virulent R20291 bacteria by amino acid depletion. Since the germination kinetics and sensitivity to the co-germinant glycine are similar for the ST1-75 and R20291 strains, our results identify the rapidity of in vivo nutrient depletion as a mechanism providing strain-specific, virulence-independent competitive advantages to different BI/NAP1/027 strains. They also suggest that the ST1-75 strain may, as a biotherapeutic agent, enhance resistance to CDI in high-risk patients. Competing Interests: Declaration of interests None.
Databáze:	MEDLINE
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